Dec. 19, 2019 — The Department of Biology’s John McCarrey is now part of a renowned group of researchers collaborating to investigate men’s reproductive health in a study through the National Center for Translational Research in Reproduction and Infertility.
McCarrey, along with the University of Nevada, Reno School of Medicine, and The Lundquist Institute at Harbor-UCLA Medical Center are now part of the newly created Center for Male Reproductive Epigenomics. As part of the center, the group will research how an unhealthy lifestyle predisposes the sperm epigenome and can affect disease susceptibility in future offspring.
McCarrey, who is also the Kleberg Distinguished University Chair in Cellular and Molecular Biology, received $1,653,856 in funding for five years to conduct his part of the research at UTSA. The funding is part of a $7 million grant awarded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development to the University of Nevada, Reno School of Medicine as the research study’s lead institution.
The newly formed center is now the eighth NCTRI center and the first to specialize in sperm epigenomics. The other centers are managed by institutions such as Cornell University, Northwestern University, Stanford University and several others.
“It’s good for UTSA to be able to be involved in these multicenter, multi-institutional efforts that involve prestigious places around the country,” McCarrey said. “It bodes well for how our research enterprises are growing and succeeding. The difference between now and when I came here 20 years ago is amazing. The amount of research that's going on here now and the level of research across the board have really grown.”
Together the researchers plan to investigate “the impact of lifestyle on the integrity of the sperm epigenome, the molecular mechanism underlying the transmission of lifestyle-induced sperm epimutations to offspring and the mechanisms by which inherited epimutations can predispose to disease states in offspring,” McCarrey said.
“This effort will involve two parallel studies focused on male mice and a group of adult men,” he said. “The group of men will be a mix of inactive men who maintain an unhealthy lifestyle and those with a healthy diet and exercise lifestyle. The men will follow a controlled regimen in terms of diet and exercise while their weight is monitored and blood and semen samples are collected.”
The researchers are also looking at the effect a high-fat diet without exercise or a normal diet and exercise have on male mice.
“The mice are going to be either on a high fat diet or a healthy diet and they are going to either have access to a running wheel to provide exercise or not,” McCarrey said. “We will then breed these mice to generate offspring in order to measure the effects the father’s diet and exercise habits may have on the health of his offspring.”
With the information gathered, McCarrey plans to look at epigenetic programming in germ cells from both the male mice and men.
During his research, McCarrey will pursue questions such as how diet and exercise affect the sperm epigenome and to what extent does an unhealthy diet and/or lack of exercise have the potential to disrupt the normal pattern of epigenetic programming in the sperm of male mice or men.
Furthermore, he’ll look into what extent can lifestyle habits disrupt not only epigenetic programming in the sperm of these males but also in the somatic tissues or the germ cells in their offspring.
According to McCarrey, when an environmental exposure or an unhealthy lifestyle initially disrupt the epigenome in an exposed individual it typically starts in somatic cells in the body from there, these disruptions are somehow into the germ line that will produce sperm in males or eggs in females. But it’s unknown how these epigenetic disruptions transition from somatic cells to germline cells.
“As a result, unhealthy lifestyles or exposures to environmental disruptors can be inherited by the next generation and even by the next four or five generations, even though these subsequent generations have not, themselves, been exposed to the original disruptive influence,” McCarrey said. “The only biological connection between one generation and the next is the germ cells. We often hear about how certain things such as diet, exercise, alcohol, or drugs can affect the fetus during a woman’s pregnancy, but it is rare to hear people talking about how the lifestyle of the father can also affect the child.”
“It is often assumed fathers only have to provide the information carried in the sperm and that there is no further impact of the father’s lifestyle on his offspring, however that is not the case,” McCarrey said.
“In fact, the father’s lifestyle prior to contributing the sperm that generates the new baby can significantly impact the entire life of the offspring,” McCarrey said.
Once McCarrey and the other researchers are done with the current project, he said they hope to further their work beyond this initial five-year project to further study how the effects of a father’s lifestyle can impact the health of his children, grandchildren and beyond.
“This new grant provides an opportunity for my lab to be involved with a group that together can-do things that none of us could do by ourselves,” McCarrey said. “This will allow me to pursue some of these questions in ways that I could never have done by myself.”
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